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Natural Bioactive Thiazole-Based Peptides from Marine Resources: Structural and Pharmacological Aspects

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Natural Bioactive Thiazole-Based Peptides from Marine Resources: Structural and Pharmacological Aspects marine drugs Review Natural Bioactive Thiazole-Based Peptides from Marine Resources: Structural and Pharmacological Aspects 1, , 2, , 3 4 Rajiv Dahiya * y , Sunita Dahiya * y, Neeraj Kumar Fuloria , Suresh Kumar , Rita Mourya 5, Suresh V. Chennupati 6, Satish Jankie 1, Hemendra Gautam 7, Sunil Singh 8, Sanjay Kumar Karan 9, Sandeep Maharaj 1, Shivkanya Fuloria 3, Jyoti Shrivastava 10, Alka Agarwal 11, Shamjeet Singh 1, Awadh Kishor 12, Gunjan Jadon 13 and Ajay Sharma 14 1 School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad & Tobago; [email protected] (S.J.); [email protected] (S.M.); [email protected] (S.S.) 2 Department of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00936, USA 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Semeling, Bedong 08100, Kedah, Malaysia; [email protected] (N.K.F.); [email protected] (S.F.) 4 Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra 136119, Haryana, India; sureshmpharma@rediffmail.com 5 School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, P.O. Box 196, Gondar 6200, Ethiopia; [email protected] 6 Department of Pharmacy, College of Medical and Health Sciences, Wollega University, P.O. Box 395, Nekemte, Ethiopia; sureshchennupati@rediffmail.com 7 Arya College of Pharmacy, Dr. A.P.J. Abdul Kalam Technical University, Nawabganj, Bareilly 243407, Uttar Pardesh, India; [email protected] 8 Department of Pharmaceutical Chemistry, Ideal Institute of Pharmacy, Wada, Palghar 421303, Maharashtra, India; [email protected] 9 Department of Pharmaceutical Chemistry, Seemanta Institute of Pharmaceutical Sciences, Jharpokharia, Mayurbhanj 757086, Orissa, India; sanjay_karan21@rediffmail.com 10 Department of Pharmaceutical Chemistry, The Oxford College of Pharmacy, Hongasandra, Bangalore 560068, Karnataka, India; [email protected] 11 Department of Pharmaceutical Chemistry, U.S. Ostwal Institute of Pharmacy, Mangalwad, Chittorgarh 313603, Rajasthan, India; [email protected] 12 Department of Pharmaceutical Biotechnology, Shrinathji Institute of Pharmacy, Nathdwara 313301, Rajsamand, Rajasthan, India; [email protected] 13 Department of Pharmaceutical Chemistry, Shrinathji Institute of Pharmacy, Nathdwara 313301, Rajsamand, Rajasthan, India; [email protected] 14 Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi 110017, India; [email protected] * Correspondence: [email protected] (R.D.); [email protected] (S.D.); Tel.: +1-868-493-5655 (R.D.); +1-787-758-2525 (ext. 5413) (S.D.) These authors contributed equally to this work. y Received: 25 May 2020; Accepted: 19 June 2020; Published: 24 June 2020 Abstract: Peptides are distinctive biomacromolecules that demonstrate potential cytotoxicity and diversified bioactivities against a variety of microorganisms including bacteria, mycobacteria, and fungi via their unique mechanisms of action. Among broad-ranging pharmacologically active peptides, natural marine-originated thiazole-based oligopeptides possess peculiar structural features along with a wide spectrum of exceptional and potent bioproperties. Because of their complex nature and size divergence, thiazole-based peptides (TBPs) bestow a pivotal chemical platform in drug Mar. Drugs 2020, 18, 329; doi:10.3390/md18060329 www.mdpi.com/journal/marinedrugs Mar. Drugs 2020, 18, 329 2 of 43 discovery processes to generate competent scaffolds for regulating allosteric binding sites and peptide–peptide interactions. The present study dissertates on the natural reservoirs and exclusive structural components of marine-originated TBPs, with a special focus on their most pertinent pharmacological profiles, which may impart vital resources for the development of novel peptide-based therapeutic agents. Keywords: azole-based peptide; marine sponge; peptide synthesis; cytotoxicity; cyanobacteria; thiazole; bioactivity 1. Introduction Heterocycles are known to govern a lot of processes of vital significance inside our body, including transmission of nerve impulses, hereditary information, and metabolism. A variety of the naturally occurring congeners, including reserpine, morphine, papaverine, and quinine, are heterocycles in origin, and many of the synthetic bioactives viz. methotrexate and isoniazid contain heterocyclic pharmacophores [1]. Among heterocycles, thiazoles have received special attention as promising scaffolds in the area of medicinal chemistry because this azole has been found alone or incorporated into the diversity of therapeutic active agents such as sulfathiazole, combendazole, niridazole, fanetinol, bleomycin, and ritonavir, which are associated with antibiotic, fungicidal, schistozomicidal, anti-inflammatory, anticancer, and anti-HIV properties [2,3]. Peptides are bioactive compounds of natural origin available in all living organisms and are known for their vital contribution in a wide array of biological activity. Due to their therapeutic abilities, peptides have received growing interest in recent years. In the human body, peptides perform a lot of essential functions including the engagement of peptide hormones like insulin, glucagon-like peptide-1 (GLP-1), and glucagon and in blood glucose regulation and are used to treat novel targets for certain disease conditions, including Alzheimer’s disease, diabetes mellitus type 2, and obesity [4–7]. As unique structural features make azole-containing heterocyclic peptides (especially thiazoles) attractive lead compounds for drug development as well as nice tools for advance research, efforts should be made by scientists to develop biologically active thiazole-based peptide derivatives (TBPs). TBPs are obtained from diverse resources, primarily from cyanobacteria, sponges, and tunicates. A thiazole ring can be part of a cyclic structure or connected in a linear chain of peptides either alone or with other heterocycles like oxazole (e.g., thiopeptide antibiotics), imidazole, and indole (in the forms of histidine and tryptophan), thiazoline, oxazoline, etc. Cyclic peptides have an advantage over their linear counterparts as cyclization offers a reduction in conformational freedom, resulting in higher receptor-binding affinities. Understanding the structure–activity relationship (SAR), different modes of action, and routes of synthesis as tools are of vital significance for the study of complex molecules like heterocyclic bioactive peptides, which have a broad spectrum of pharmacological activities associated with them. Further, the sudden increase in the number of peptide drug products is another good reason to study this particular category of compounds on a priority basis. Keeping in view the vital significance of TBPs, the current article focuses on different bioactive marine-derived thiazole-based polypeptides with complex structures and their potent resources, synthetic methodologies, stereochemical aspects, structural activity relationships, diverse modes of action, and bioproperties. 1.1. Resources Various natural sources of TBPs and other heterocyclic rings containing cyclopolypeptides comprise cyanobacteria [8–40], ascidians [41–62], marine sponges [63–70], and sea slugs [71–73]. Moreover, actinomycetes, sea hare, red alga, and higher plants [74–80] were found to be other potential resources of TBPs. Mar. Drugs 2020, 18, 329 3 of 43 1.2. Linear vs. Cyclic Peptides In linear peptides with amino acid units between 10 to 20, secondary structures like α-helices and β-strands begin to form, which impose constraints that reduce the free energy of linear peptides. Compared to linear peptides, cyclopeptides are typically considered to have even greater potential as therapeutic agents due to their increased chemical and enzymatic stability, receptor selectivity, and improved pharmacodynamic properties. Although peptide cyclization generally induces structural constraints, the site of cyclization within the sequence can affect the binding affinity of cyclic peptides. Cyclization is a well-known technique to increase the potency and in vivo half-life of peptide molecules by locking their conformation. Hence, both the biological activity and the stability of peptides can be improved by cyclization. The reduction in conformational freedom brought about by cyclization often results in higher receptor-binding affinities. Overall, cyclization of peptides is a vital tool for structure–activity studies and drug development because ring formation limits the flexibility of the peptide chain and allows for the induction or stabilization of active conformations. Moreover, cyclic peptides are less sensitive to enzymatic degradation [81]. The cyclization process often increases the stability of peptides, can prolong their bioeffect, and can create peptides with the ability to penetrate tumors in order to enhance the potency of anticancer drugs [82,83]. Cyclization is envisioned to enhance the selective binding, uptake, potency, and stability of linear precursors. The prolonged activity may even be the result of additional resistance to enzymatic degradation by exoproteases. Cyclic peptides are of considerable interest as potential protein ligands and might be more cell permeable than their linear counterparts due to their reduced conformational flexibility. Further, cyclic nature
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